Hormonal responsiveness of several systems has been shown to vary as a function of the substratum with which cells are associated. This phenomenon is being studied in vivo and in vitro by characterizing steroid receptor levels, hormonal responsiveness and the effect of an inhibitor of extracellular matrix collagen deposition on NMU-induced rat mammary tumors. The primary NMU-tumors have deposition on NMU-induced rat mammary tumors. The primary NMU-tumors have estrogen receptors and exhibit estrogen responsiveness in vivo. Estrogen receptor levels were found to irreversibly diminish to 20% of the original levels during collagenase for tumor cell isolation. This effect was not due to an irreversible loss of collagen production by the cells since collagen synthesis resumed in culture while estrogen receptor levels remained low and since collagenase digestion at 30 degrees C rather than 37 degrees C nearly completely prevented the loss of estrogen receptor levels. The tumor cell growth was inhibited by a selective block of collagen matrix formation in vivo and in vitro. This inhibition in response to cis-hydroxyproline was shown to be specific since transplantable NMU-tumors and MCF-7 cells did not synthesize type IV collagen and were resistant to cis-hydroxyproline.